Method of producing 1,2-dihydro-1,4-benzodiazepines-2-ones



United States Patent 3,513,159 METHOD OF PRODUCING 1,2-DIHYDRO-1,4-

BENZODIAZEPINES-Z-ONES Hjarne Paul Correll Dyrsting, Virum, Denmark, assignor to A/ S Dumex (Dumex Ltd.), Copenhagen, Denmark, a Danish company No Drawing. Filed Aug. 28, 1967, Ser. No. 663,499 Claims priority, application Denmark, Sept. 9, 1966, 4,662/ 66 Int. Cl. C07d 41/08 U.S. Cl. 260-2393 2 Claims ABSTRACT OF THE DISCLOSURE The invention relates to a novel method of producing l-alky] 1,2 dihydro 3H 5 phenyl-1,4-benzodiazepin- 2-ones by oxidizing the corresponding 1,2,4,5-tetrahydro compounds with azodicarboxylic acid diethyl ester.

This invention relates to a method of producing l-alkyl- 1,Z-dihydro-3H-2-oxo-5-phenyl-1,4-benzodiazepines of the general formula R2 f 1 XQ /C]EI2 I R (I) wherein X represents hydrogen, halogen, a nitro group, a nitroso group, an alkyl group, a trifluoromethyl group or a hydroxy group, R represents a phenyl group, which may be substituted, and R represents a lower alkyl group, preferably a methyl group.

It is known that 1,4-benzodiazepines of the general formula \CH-NH R (II) wherein X and R are as hereinbefore described, can be oxidized by means of common oxidizing agents, such as CrO to establish a double bond in the 4,5-position.

If, however, the nitrogen atom in the l-position is substituted with an alkyl group, for example a methyl group, it has not hitherto been possible, by means of the usual oxidizing agents, to accomplish an oxidation to introduce the said double bond, since the oxidation in that case goes on to yield mainly the corresponding 2,3-dioxo compound (J. Org. Chem., 30 (1965), 1308).

According to the present invention it has now surprisingly been found that the compounds of Formula I above can be produced by reacting a compound of the general formula 3,513,159 Patented May 19, 1970 wherein X, R and R are as hereinbefore defined, with the diethyl ester of azodicarboxylic acid, according to the following scheme of reaction:

The reaction proceeds smoothly, swiftly, and completely quantitatively, which is a great advantage, because the purification problems are avoided, which are characteristic for the oxidation methods using common oxidizing agents as mentioned hereinbefore.

In a preferred embodiment of the present method 1- methyl 1,2,4,5 tetrahydro 5 phenyl 3H 7 chloro- 1,4-benzodiazepin-2-one is oxidized to 1-methyl-1,2-dihy dro-S-phenyl-3H-7-chloro-1,4-benzodiazepin 2 one by means of azodicarboxylic acid diethyl ester.

As is known, the compounds resulting from the present method, and especially the above identified compound, are of strongly sedative and tranquilizing effect.

The present method is illustrated by the following example.

EXAMPLE To 1.4 g. of l-methyl-l,2,4,5-tetrahydro-5-phenyl-3H-7- chloro-1,4-benzodiazepin-2-one dissolved in 20 ml. of dry benzene are added 0.87 g. of azodicarboxylic acid diethyl ester.

The mixture is refluxed for one hour and left overnight at room temperature. The precipitated crystals of hydrazodicarboxylic acid diethyl ester are sucked off, yielding 0.7 g. of MP. -133 C. The benzene solution is evaporated in vacuo to dryness. The residue is dissolved in 10 ml. of boiling isopropanol. By cooling the solution, 1.1 g. of l-methyl-l,Z-dihydro-S-phenyl-3H-7-chloro-1,4-benzodiazepin-Z-on of MP. 128130 C. are precipitated.

I claim:

1. Method of producing l-alkyl-1,2-dihydro-3H-5-phenyl-1,4-benzodiazepin-2-ones of the formula wherein X is a member of the group consisting of hydrogen, and halogen, R is a phenyl group, and R is a lower alkyl group, comprising the step of oxidizing a compound of the formula R2 1 Ic=0 X 011:

\(JHNH R (III) wherein X, R and R are as above defined, with azodicarboxylic diethyl ester.

2. The method of claim 1, in which the starting mate- 4 rial is l-rnethyl-1,2,4,5-tetrahydro-5-phenyl-3H-7-chlorol,4-benzodiazepin-2-one.

References Cited UNITED STATES PATENTS 3,371,085 2/1968 Reeder et a1 260--239.3

HENRY R. JILES, Primary Examiner R. T. BOND, Assistant Examiner US. Cl. X.R. 260-192, 482, 999 

